monoclonal antibody. AMG 334 is a fully human monoclonal antibody under investigation for the prevention of migraine. AMG 334 inhibits Calcitonin-Gene-Related-Peptide (CGRP) by targeting its receptor, rather than CGRP itself, which is believed to transmit signals that can cause incapacitating pain.

AMG 334 is currently under investigation in several large global, randomized, double-blind, placebo-controlled studies to evaluate its safety and efficacy in migraine prevention.

In August 2015, Novartis entered into a global collaboration with Amgen to commercialize and develop new treatments in the field of Alzheimer's disease and migraine, including AMG 334 (currently in phase III studies for episodic migraine and a phase II study for chronic migraine) and AMG 301 (currently in a phase I study for migraine). As part of the collaboration, Amgen retained commercialization rights in the U.S., Canada and Japan, and Novartis has rights in Europe and the rest of the world.

Aimovig™ is the first investigational therapy targeting the CGRP pathway to receive FDA and European Medicines Agency regulatory filing acceptance. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018 . If approved, it will be administered once-monthly using a self-injection device. If approved, Novartis and Amgen will co-commercialize Aimovig in the U.S. Amgen has exclusive commercialization rights to the drug in Japan and Novartis has exclusive rights to commercialize in rest of world.

LIBERTY is a Phase 3b, multicenter, randomized 12-week, double-blind, placebo-controlled study evaluating the safety and efficacy of Aimovig™ in patients with episodic migraine (defined in the trial as four to 14 migraine days per month at baseline) who have failed up to four prior preventive treatments for migraine. In the study, 246 participants with episodic migraine who had two to four previous treatment failures were randomized to receive Aimovig™ 140 mg or placebo during the 12-week double-blind treatment phase. The primary endpoint was the percentage of patients with at least a 50 percent reduction of monthly migraine days from baseline over the last four weeks of the double-blind treatment phase of the study (weeks 9-12).1 The study includes an ongoing 52-week open-label extension study.

Secondary endpoints assessed during the same time period included: change from baseline in monthly migraine days, change from baseline in the number of monthly acute migraine-specific medication treatment days, and change from baseline in the MPFID physical impairment and impact on everyday activities domain scores. The MPFID is a scale developed to measure these two domains. The scale has been validated in line with FDA Patient Reported Outcomes Guidance.2 Percentages of patients with a 75 percent response rate and 100 percent response rate to erenumab were also assessed as secondary endpoints. (NCT03096834)

Latest
news:

• On October 23, 2018, Novartis announced that the full data from the LIBERTY study of Aimovig® (erenumab) in episodic migraine patients who had tried and failed two to four prior preventive treatments have been published in The Lancet. Patients treated with Aimovig® had significant improvements on all primary and secondary endpoints of the study. The LIBERTY data show that, compared to placebo, from baseline to the last month of therapy (weeks 9-12):

The primary endpoint showed that more than twice as many patients on Aimovig® had their migraine days cut by 50% or more (30% vs.14%; odds ratio 2.7, p=0.002)

Almost three times as many patients on Aimovig® had their migraine days cut by 75% or more (12% vs. 4%; odds ratio 3.2, p=0.025, secondary endpoint)

6% of patients on Aimovig® were completely migraine free (migraine days cut by 100%) vs no patients (0%) on placebo (secondary endpoint)

Those in the Aimovig® arm reported significant reductions in the number of days per month using acute migraine-specific medication (1.3 reduction vs 0.5 day increase; p<0.001, secondary endpoint).

Overall, the tolerability and safety profiles for Aimovig® were similar to placebo, in keeping with findings throughout the drug's clinical trial program of over 3,000 patients

The patients in LIBERTY, who had tried multiple treatments without success, represent a section of the migraine community which is highly impacted by the disease in all areas of life. Of note, the recent My Migraine Voice study showed that patients with multiple prior treatment failures reported the greatest impact on work productivity compared to those who had not previously tried treatments without success. Moreover, a higher proportion of these patients reported a negative impact on their social and personal life.

• On April 17, 2018, Amgen announced full results from the Phase 3b LIBERTY trial of Aimovig™ (erenumab) in episodic migraine patients who had previously failed two to four preventive treatments, due to lack of efficacy or to intolerable side effects. The data, which will be presented at the 70th Annual Meeting of the American Academy of Neurology (AAN) in Los Angeles , show the potential of Aimovig™ as an effective preventive treatment option for these patients, who have tried several treatment options without gaining relief.

In LIBERTY, 246 patients who had experienced two to four previous preventive treatment failures were randomized to receive monthly subcutaneous injections of either Aimovig™ 140 mg or placebo for 12 weeks. Patients taking Aimovig™ had nearly three-fold higher odds of having their migraine days cut by at least 50 percent, with more than twice as many patients taking Aimovig™ achieving this reduction compared to placebo (weeks 9-12: 30.3 percent with Aimovig, 13.7 percent with placebo, p<0.002, odds ratio 2.73).

In the study, patients taking Aimovig™ also had statistically significant and clinically meaningful improvements from baseline compared to placebo across all secondary endpoints:

Over 97 percent of Aimovig patients completed the double-blind phase of the LIBERTY study. There were no adverse events leading to discontinuation of treatment in the Aimovig group, while 0.8 percent of those in the placebo group experienced adverse events leading to discontinuation of treatment.

The long-term open label extension phase of the study is ongoing. LIBERTY contributes to an extensive body of evidence, across the spectrum of migraine, in support of the efficacy, safety and tolerability profile of Aimovig. Aimovig has been studied in four placebo-controlled Phase 2 and Phase 3 clinical studies involving more than 3,000 patients and continues to be studied in an ongoing open-label extension for up to five years in duration.

• On January 22, 2018, Amgen announced positive results from the Phase 3b LIBERTY study assessing the efficacy and safety of Aimovig™ (erenumab) 140 mg in patients with episodic migraine who had experienced two to four previous preventive treatment failures, due to lack of efficacy or intolerable side effects. The study met its primary endpoint, with significantly more patients taking Aimovig™ experiencing at least a 50 percent reduction from baseline in their monthly migraine days as compared to placebo. LIBERTY also met all secondary endpoints, including reduction of monthly migraine days, reduction in days needing acute (rescue) medication, improvement in scores on the Migraine Physical Function Impact Diary (MPFID) tool, and 75 percent and 100 percent responder rates (number of patients experiencing at least a 75 percent or 100 percent reduction in monthly migraine days compared to placebo). The safety data are consistent with previous studies of Aimovig™ to date. Full data will be presented at an upcoming scientific meeting.

These results are the first positive placebo-controlled data ever reported in an episodic patient population consisting entirely of those who have tried and failed two to four preventive medications due to lack of efficacy or intolerable side effects.

The safety, efficacy and tolerability of Aimovig™ have been assessed in more than 3,000 patients, including an ongoing open-label extension of up to five years in duration.

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